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Abstract

Malakoplakia is an uncommon inflammatory condition usually affecting the genitourinary tract, which has been associated with
infections, tumors, and immunocompromised states. The condition has been reported in many different organs and it may rarely
involve the skin. We describe a case of an isolated perianal cutaneous malakoplakia in an immunocompetent 23-year-old Syrian
male.

Case report

Figure 1

A 23-year-old male with no significant medical history was referred for evaluation of three asymptomatic pink perianal nodules
that he'd had for 7 months. They were treated with surgical excision as genital condylomata, but they recurred. No systemic
medications were used. Physical examination revealed three perianal, pink, soft, non-tender, non-itching, and painless nodules,
without scar or drainage (Figure 1). His general health was otherwise good; no palpable lymph nodes were present at any site.
Routine blood tests including blood glucose and white blood cell count were within normal range. Blood tests for HIV and VDRL
were negative. Abdomen echography and chest X-ray were normal. The patient did not drink alcohol and did not take any medication
prior to his complaints.

Figure 2

Figure 3

Histopathology of one routinely stained excised nodule revealed diffuse cellular infiltrate composed predominantly of large
histiocytes with foamy cytoplasm, neutrophils, and lymphocytes (Figure 2). When a periodic acid-Schiff stain was performed,
Michaelis-Gutman bodies were evident (Figure 3) and the diagnosis of cutaneous malakoplakia was made. No culture was performed.
The treatment included local excision, ciprofloxacin 750 mg, 2 tab per day for 14 days, and ascorbic acid 500 mg/day with
good response. No recurrence was noted on follow-up after 2 months.

Discussion

Malakoplakia is an uncommon inflammatory condition usually affecting the genitourinary tract, which has been associated with
infections, tumors, and immunocompromised states [1]; it has been reported in many different organs. More than 400 cases have been described in numerous anatomic locations including
the bladder, kidney, prostate, testis, pancreas, oropharynx, retroperitoneum, thyroid gland, lymph nodes, lung, bone/joint,
and brain [2]. The majority of the lesions occur in the genitourinary tract, accounting for 60 percent to 70 percent of the cases [13, 14].

Cutaneous malakoplakia is a rare entity with less than 50 cases reported in the literature [2]. The disease was first described by Michaelis and Gutmann in 1902. In 1903, it was named 'malakoplakia' by Von Hansemann.
The term malakoplakia originates from the Greek 'malakos' (soft) and plakion (plaque). Malakoplakia of the skin was first
described by LeClerc and Bernier in 1972 [3]. However, cutaneous malakoplakia is still a rare entity. The most common reported site in the skin is the perianal area
[3], as in our case report. The lesions have been described in a variety of cutaneous sites including perineum (41% perianal,
vulva, inguinal, scrotum), abdominal wall/thorax (20%), head and neck (20% forehead, eyelid, neck), extremities (10% hands/wrist,
arm, thigh), and axilla (10%). Four cases (10%) presented with lesions involving more than one anatomic site [14, 15, 16, 17].

The pathogenesis is poorly understood, but it is thought to be secondary to an acquired bacteriocidal defect in macrophages
occurring mostly in immunosuppressed patients or in the setting of autoimmune diseases. In the reported cases of cutaneous
malakoplakia, most cases occurred in males (70%) and mainly in adults with a median age of 53 years (range, 2 months to 81
years). Many of the cases presented in the setting of organ transplantation (23%) with all occurring in kidney transplant
patients except for 1 patient who had undergone a heart transplant. Other clinical settings include patients with connective
tissue disorders (15%), neoplasm (10%), diabetes mellitus (10%), and chronic debilitating/immunodeficiency disorders such
as human immunodeficiency virus/acquired immunodeficiency syndrome, hepatitis C, sarcoidosis, and chronic immunodeficiency
disorders (18%) [2].

Malakoplakia rarely presents in patients with HIV infection and AIDS, which may be because of the preservation of monocytic
antimicrobial function in these patients. Schaller J. described a cutaneous malakoplakia in a patient with psoriasis vulgaris
[4].

The defect in malakoplakia appears to involve the function of the monocytes in endocytosis and intracellular bacterial digestion.
The Michaelis-Gutman bodies are thought to represent an accumulation of non-exocytosed phagolysosomes that have undergone
calcification [5] and contain a dense calcium hydroxyapatite core with variable amounts of iron; therefore they stain with the periodic acid-Schiff,
VonKossa, and Perls iron stain and are considered pathognomonic for malakoplakia. Studies have suggested that a decreased
intracellular cyclic guanosine monophosphate (cGMP) level may interfere with adequate microtubular function and lysosomal
activity, leading to an incomplete elimination of bacteria from macrophages and monocytes.

The most common isolated organism is Escherichia coli. However, other bacteria have been identified, including pseudomonas, proteus, klebsiella, staphylococcus, rhodococcus, and mycobacterium [6].

Clinically, lesions present as papules or plaques that are yellow to pink or skin colored, abscesses, erythematous papules,
subcutaneous nodules, ulcerations, or masses. Malakoplakia has also been associated with nonhealing surgical wounds [2] and may have associated drainage and sinus tract formation near the urethra, the thigh, the vulva, and the perianal area.
The most common presentations were mass-like lesions/nodules (45%) and abscess (18%) and ulcerations (23%) [2]. Lesions may be clinically misdiagnosed as abscess, malignancy, lymphoma, or benign skin tag.

Microscopically, malakoplakia is characterized by the presence of foamy histiocytes with distinctive basophilic inclusions,
which are known as Michaelis-Gutmann bodies because of partially ingested bacteria and calcification [7].

Treatment of malakoplakia depends on the extent of disease and the underlying condition of the patient. Antibiotics that concentrate
in macrophages (e.g., ciprofloxacin and trimethoprim-sulfamethoxazole) as well as penicillins, and clofazimine are associated
with a high cure rate [8, 9]. Antibiotic therapy directed against gram-negative bacteria, especially E. coli in combination with surgery provides the best chance of cure because excision of skin lesions and drainage of abscesses are
fundamental to diagnosis and treatment. Discontinuation of immunosuppressive drug therapy is usually required.

Other reported treatment options include ascorbic acid and bethanechol chloride, both of which are used to increase the intracellular
cylic guanosine monophosphate in an attempt to improve macrophagic function [10, 11]. Our patient responded to a combination of local excision, ascorbic acid, and antibiotic therapy.

Cutaneous malakoplakia usually has a benign clinical course, with a mean duration of skin lesions of 4-6 months. Mortality
is most often due to an underlying condition. Significant morbidity relates to the chronicity of the condition, which can
resist local and systemic therapy. Draining sinuses, persistence of disfiguring skin lesions, and involvement of visceral
organs constitute significant morbidity in patients with malakoplakia.